Evaluation of an alternative S100b assay for use in cardiac surgery: relationship with microemboli and neuropsychological outcome

INTRODUCTION: The aim of the study was to investigate the relationship between S100b release, neuropsychological outcome and cerebral microemboli. Peri-operative assay of the astroglial cell protein S100b has been used as a marker of cerebral damage after cardiac surgery but potential assay cross-reactivity has limited its specificity. The present study uses an alternative enzyme-linked immunoabsorbant assay (ELISA) for serum S100b that has documented sensitivity and specificity data in patients undergoing coronary artery bypass grafting (CABG). METHODS: Fifty-five consecutive patients undergoing routine CABG surgery received serial venous S100b sampling at five time points: i) Pre-operative, ii) At the end of cardiopulmonary bypass (CPB), iii) 6 hrs, iv) 24 hrs and v) 48 hrs post skin closure. A previously described sandwich ELISA with monoclonal anti- S100b was used. This assay has a lower limit of detection of 0.04 microg/L and < 0.006% reactivity with S100a at a concentration of 100 microg/L S100a. Cerebral microemboli during surgery were recorded by transcranial Doppler monitor over the right middle cerebral artery. Evidence of cerebral impairment was obtained by comparing patients' performance in a neuropsychological battery of 9 tests administered 6-8 weeks post-operatively with their pre-operative scores. RESULTS: There was a significant increase in S100b only at the end of bypass (mean 0.30 microg/L, SD +/- 0.33 and range .00 to 1.57). S100b levels at the end of bypass did not correlate with neuropsychological outcome or microemboli counts. CONCLUSIONS: The low levels of S100b detected using the present assay, despite its high sensitivity and despite the routine use of cardiotomy suction, suggest that the assay may have higher specificity for cerebral S100b than previously used assays. There was no evidence that this assay is related to neuropsychological change or cerebral microemboli in cardiac surgery.     

Use of a dynamic bubble trap in the arterial line reduces microbubbles during cardiopulmonary bypass and microembolic signals in the middle cerebral artery

Neurological complications remain an important cause of morbidity and mortality of patients following cardiopulmonary bypass (CPB). Microemboli, as well as cerebral hypoperfusion, are the main postulated mechanisms. This study demonstrates that the insertion of a dynamic bubble trap (DBT) into the curcuit reduces microbubbles in the arterial line and microembolic signals (MES) in the middle cerebral arteries (MCAs). We investigated 12 patients during coronary artery bypass grafting (CABG). The DBT was inserted between the arterial filter and the arterial cannula. For detection of microemboli before and after the DBT, a special ultrasound Doppler device was used. MES were detected by transcranial Doppler monitoring in both MCAs of the patients. Microbubbles and MES were counted during bypass. These data were compared to 12 patients who were operated in a previous period without the use of a DBT. There were no significant differences in both groups with respect to gender, age, crossclamp and bypass time and number of anastomoses. In the group without a DBT in the circuit, a mean of 6311 microbubbles per operation could be observed distal to the arterial filter, corresponding to 282 MES. After inclusion of a DBT, we could register, in the second group, 8496 microemboli proximal and 2915 distal of the DBT, corresponding to 89 MES per operation. The reduction rate of microbubbles in the tubing was 65.7%, corresponding to a reduction in MES of about 86.2%. We conclude that the insertion of a DBT in the arterial line of CPB circuit protects the cerebrovascular system from microembolic events, as demonstrated by lower MES counts.     

Direct measurement of nitric oxide during experimental cardiopulmonary bypass

We developed a system to measure nitric oxide (NO) concentration during cardiopulmonary bypass in anaesthetized pigs (n = 6). A T-shaped connector, attached to an NO sensor, was mounted in the extracorporeal circuit at two measuring sites: proximal to the membrane oxygenator (venous side) and distal to the arterial line filter (arterial side). After performing a preliminary validation study, we measured plasma NO concentration before and during total cardiopulmonary bypass circulation (non-pulsatile flow 1.5 l/min) and without pulmonary ventilation. After establishing bypass, PaO2 was 318 - 393 mmHg; when PaO2 was decreased to 80 - 100 mmHg, plasma NO concentration in the arterial circuit fell by 39.2 +/- 15.6 nM. There was no observable change in plasma NO concentration at the venous circuit. This new system could be useful in monitoring NO concentration during cardiac surgery with cardiopulmonary bypass, and for understanding the possible pathophysiological roles of hyper-nitric oxaemia in cardiopulmonary bypass-related cardiovascular complications.     

Evaluation of Quadrox-i and Capiox FX neonatal oxygenators with integrated arterial filters in eliminating gaseous microemboli and retaining hemodynamic properties during simulated cardiopulmonary bypass

Perfusion quality during cardiopulmonary bypass (CPB) procedures can contribute to postoperative neurological complications and influence patient recovery and outcome. Gaseous microemboli generated in the circuit and hemodynamic properties of blood reaching the patient can be monitored during CPB to optimize perfusion. Oxygenators that oxygenate the blood during CPB can significantly influence the quality of blood reaching the patient by their manufacturing designs. New hollow-fiber membrane oxygenators are developed with integrated arterial filters to reduce priming volume and eliminate a separate arterial filter in the circuit. To evaluate the performance of these new oxygenators, we used a simulated model to compare the Quadrox-i Neonatal and the Capiox Baby FX05 neonatal oxygenators and to provide a review of these oxygenators with their respective counterparts which have separate arterial filters. We found that microemboli counts for the new Quadrox-i and Capiox FX05 oxygenators are similar in the arterial line, but different across the oxygenator for all experimental conditions. The arterial purge line diverting blood from the patient reduces microemboli count for the Capiox FX05, but is inconsistent for the Quadrox-i Neonatal. While hemodynamic energy delivered to the patient is similar for both oxygenators, shunted blood flow for the Quadrox-i Neonatal oxygenator is three times higher than the Capiox FX05 (103.6 mL/min vs 33.0 mL/min at 400 mL/min and 35°C) (p<0.001).     

Neurological and neuropsychological examination and outcome after use of an intra-aortic filter device during cardiac surgery

Cerebral embolization of particles after cardiac surgery is frequently associated with neurological deficits. Aortic crossclamp manipulation seems to be the most significant cause of emboli release during cardiac surgery. The goal of this study was to demonstrate whether the use of an intra-aortic filter device has an effect on the magnet resonance imaging (MRI) and functional neurological outcome. Twenty-four patients undergoing cardiosurgical procedures using cardiopulmonary bypass (CPB) were selected: coronary artery bypass graft (CABG) surgery (n = 17), aortic valve replacement (AVR) surgery (n = 4) or combined procedures (n = 3). Patients were evaluated by diffusion weighted MRI of the brain, neurological examination and neuropsychological assessment regarding alertness as well as divided and selective attention before and five to seven days after surgery. The patients were divided into two groups. In group I, 12 patients received a filter through a modified 24 F arterial cannula immediately before the aortic crossclamp was released. Filters remained in the aorta until CPB was discontinued. Intraoperatively, bilateral middle cerebral artery transcranial Doppler (TCD) was monitored at baseline, at the beginning of CPB, at a timepoint when the aorta was crossclamped, when the filter was inserted and while the crossclamp was switched to partial clamping until the CPB was discontinued. TCD was used for detection of microembolic signals (MES). The captured material in the filter was examined histologically. Twelve patients served as controls without aortic filtration (group II). The MRI of the brain did not show any diffusion alterations in either group before or after surgery. No patient developed a focal neurological deficit or stroke. Intraoperative quantitative MES detection revealed a four to tenfold increase in patients of group I compared with group II (5-6 versus 0.5-1 MES/min) during the filter dwell time. There was no consistent pattern regarding the neurobehavioural sequelae. Filters showed arteriosclerotic debris in 75% of the patients. The use of the intra-aortic filter device did not show a positive effect on neurological, neuroradiographical and neuropsychological outcomes. The increase of the MES rate in group I patients may be due to microbubbles generated as microcavitations by the filter or the aortic filter cannula. The intra-aortic filter was able to capture atheromatous material in 75% of the patients.     

Comparison of the effects of pulsatile cardiopulmonary bypass, non-pulsatile cardiopulmonary bypass and off-pump coronary artery bypass grafting on the inflammatory response and S-100beta protein

Background: We aimed to investigate the effects of off-pump coronary artery bypass grafting, pulsatile cardiopulmonary bypass, and non-pulsatile cardiopulmonary bypass techniques on the inflammatory response and the central nervous system in the current study. Methods: A total of 32 patients who were scheduled for elective coronary artery bypass graft surgery were included in the study. The patients were allocated into three different groups according to the perfusion techniques used during the cardiopulmonary bypass procedure as follows: off-pump coronary artery bypass grafting group (n=10); pulsatile cardiopulmonary bypass group (n=11); and non-pulsatile cardiopulmonary bypass group (n=11). Serum interleukin-6, interleukin-8, tumor necrosis factor-alpha and S-100beta levels were measured preoperatively, and at 0, 6, and 24 hours postoperatively. Results: The postoperative increase in the levels of interleukin-6 and interleukin-8 was significantly lower in the off-pump group compared to the other two groups (p<0.05), while there was no significant difference in tumor necrosis factor-alpha levels between the groups. Postoperative S-100β levels, an indicator of cerebral injury, was significantly lower in the off-pump CABG group compared to the other two groups (p<0.05). Conclusion: We found that off-pump coronary artery bypass grafting had less negative effects on inflammatory response and central nervous system compared to pulsatile cardiopulmonary bypass and non-pulsatile cardiopulmonary bypass techniques.     

Should we rely on nasopharyngeal temperature during cardiopulmonary bypass?

A potential morbidity of incomplete re-warming following hypothermic cardiopulmonary bypass (CPB) is cardiac arrest. In contrast, attempts to fully re-warm the patient can lead to cerebral hyperthermia. Similarly, rigid adherence to 37.0 degrees C during normothermic CPB may also cause cerebral overheating. The literature demonstrates scant information concerning the actual temperatures measured, the sites of temperature measurement and the detailed thermal strategies employed during CPB. A prospective, randomized, controlled study was undertaken to investigate the ability to manage perfusion temperature control in a group of hypothermic patients (28 degrees C) and a group of normothermic patients (37 degrees C). Eighty patients presenting for first-time, elective coronary artery bypass graft surgery (CABG) were randomly allocated to the hypothermic and normothermic groups. All surgery was performed by one surgeon and the anaesthesia managed by one anaesthetist. Temperature measurements were made at the nasopharyngeal (NP) site, as well as in the arterial line of the CPB circuit. The hypothermic group had the arterial blood temperature lowered to 25.0 degrees C to maintain the NP temperature at 28.0-28.5 degrees C. During re-warming, the arterial blood was raised to 38.0 degrees C. Meanwhile, in the normothermic group, the arterial blood temperature was raised to a maximum of 37.0 degrees C to maintain NP temperature at 36.5-37.0 degrees C. Despite strict guidelines, some patients transgressed the temperature control limits. Two patients in the hypothermic group failed to reach an NP temperature of 28.5 degrees C. Twenty-six patients were managed entirely within the control limits. During rewarming in both groups, control of both arterial and NP temperature was well managed with only 25% patients breaching the respective upper control limits. During the re-warming phases of CPB, we were unable to make any correlation between NP temperature and arterial blood temperature, using body weight or body mass index as predictors. Based on the results obtained, we recommend that strict criteria should be implemented for the management of temperature during CPB, in conjunction with more emphasis being placed on monitoring arterial blood temperature as a marker of potential cerebral hyperthermia. We should, therefore, not rely on NP temperature measurement alone during CPB.     

Ex vivo testing of the Quart arterial line filter

Arterial line filters are now routinely used in cardiac surgery in order to decrease the microemboli load to the patient. The Quart filter (Jostra, Hirrlingen, Germany) with a new planar construction design, an easy de-airing system and an integrated bypass, was tested for air filtration capacity and resistance to blood path in a standardized setting with surviving animals. Three calves (mean body weight: 71+/-3.4 kg) were connected to a standard cardiopulmonary bypass (CPB) circuit by jugular venous and carotid arterial cannulation with a mean flow rate of 3.5 l/min. The arterial line filter was challenged with upstream injections of boluses of air of 5, 10 and 15 ml, respectively. A Doppler ultrasound was positioned downstream on the arterial line to measure bubble count and size. The pressure drop through the filter was monitored at flow rates of between 1 and 6 l/min. At the end of the procedure the animals were weaned from the CPB and, thereafter, from the ventilator. After 7 days, the animals were sacrificed electively. This study shows that important quantities of air can be injected into the arterial line upstream of the filter with small volumes of small sized bubbles recorded downstream. With the 5 ml air bolus injection, mean values of 0.3+/-0.6 bubbles of 30 and 40 microm were detected, whereas with the 20 ml bolus, 32.6+/-8.7 bubbles of 10 microm, 3.7+/-1.1 bubbles of 30 microm, 3.3+/-0.6 bubbles of 40 microm and 0.7+/-1.1 bubbles of 50 microm were recorded. The blood path resistance at different blood flow rates was well within the acceptable range with a pressure drop of 20+/-0 and 26.6+/-5.7 mmHg at flow rates of 4 and 5 l/min, respectively. With its planar concept, the Quart filter offers good air filtering capacity both in terms of bubble count and size after injection of large boluses of air, without any increase of resistance to the blood path. Moreover, it offers a venting function and an integrated bypass system.     

The use of leucocyte-depleting and conventional arterial line filters in cardiac surgery: a systematic review of clinical studies.

Although various forms of arterial line filter have been available for use during cardiopulmonary bypass (CPB) for 30 years, their use is not universal. The aim of this review was to seek evidence of the clinical benefit of using conventional or leucocyte-depleting arterial line filters during bypass. A literature search revealed 28 relevant clinical studies. Despite the wide variety of patient populations, types of filter and outcome measures utilized in studies, a few conclusions are possible. Whereas conventional filtration has the definite effect of reducing neuropsychological deficit post-CPB, the results of studies using the leucocyte-depleting filter are less clear cut. Leucocyte-depleting filters have potential for reducing inflammatory mediated heart and lung injury, however it is recommended that any additional benefit of leucocyte-depleting filters over conventional filters should be further tested by randomized controlled trials of sufficient size.     

An increase in urinary nitrite/nitrate excretion is associated with the hyperdynamic state after cardiovascular surgery

OBJECTIVES: To test the hypotheses (1) that nitric oxide (NO) production is stimulated after cardiovascular surgery and is related to the hyperdynamic state and (2) that NO production is more prominent in patients with cardiopulmonary bypass. DESIGN: Prospective, clinical study. SETTING: Intensive care unit in a university hospital. PATIENTS: One hundred patients after cardiovascular surgery: coronary artery bypass graft with (n=53) and without (n=17) cardiopulmonary bypass, valve surgery with cardiopulmonary bypass (n=23) and thoracic aortic replacement with cardiopulmonary bypass (n=7). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Urinary nitrite/nitrate (NOx) excretion was measured by the high-performance liquid chromatography-Griess system as an index of endogenous NO production during the first 2 postoperative days. Hemodynamic variables, hematologic variables and serum C-reactive protein concentrations were measured after the operation. Urinary NOx concentrations were 146+/-70 and 190+/-93 micro mol/l, and the amounts of NOx excreted in the urine were 23+/-10 and 18+/-8 micro mol/h on the 1st and 2nd days, respectively. Urinary NOx excretions were positively correlated with the cardiac index (P<0.01), but inversely correlated with the systemic vascular resistance index (P<0.01). Urinary NOx concentrations were positively correlated with serum C-reactive protein concentrations (P<0.01), but inversely correlated with the cardiopulmonary bypass time (P<0.01). The urinary NOx concentration was highest in patients undergoing coronary artery bypass graft without cardiopulmonary bypass. CONCLUSION: These findings suggest, firstly, that NO production is stimulated by a surgical inflammatory response and, secondly, that the endogenous NO contributes to the increase in cardiac output that accompanies the reduced systemic vascular resistance after cardiovascular surgery.     

Cerebral blood flow pattern and autoregulation during open-heart surgery in infants and young children: a transcranial, Doppler ultrasound study.

OBJECTIVES: To elucidate the effect of cardiopulmonary bypass on cerebral perfusion and on the autoregulatory ability of the cerebral vascular bed of infants and young children. SETTING: Operating room. DESIGN: Prospective study. PATIENTS: Thirteen newborn infants and young children undergoing open-heart surgery. INTERVENTIONS: Cerebral blood flow velocity was monitored in the patients undergoing open-heart surgery from just before the induction of anesthesia until the discontinuation of anesthesia after completion of the surgery. MEASUREMENTS AND MAIN RESULTS: Cerebral blood flow velocity was assessed by semicontinuous measurement of temporal mean blood flow velocity in the middle cerebral artery using a range-gated, pulsed Doppler flowmeter with a transducer that was firmly attached to the left temporal region of the head. Mean arterial pressure (MAP) and nasopharyngeal temperature were continuously monitored. During hypothermic (18.4 degrees C to 31.9 degrees C) cardiopulmonary bypass, cerebral blood flow velocity decreased and showed a close relationship with nasopharyngeal temperature (p less than .0001). During steady-state cardiopulmonary bypass, cerebral blood flow velocity showed a correlation with MAP (p less than .01). The nasopharyngeal temperature influenced this relationship: at lower (absolute) nasopharyngeal temperatures, lack of cerebral autoregulation was more common. CONCLUSIONS: The finding suggests that cerebral blood flow decreases with decreasing nasopharyngeal temperature. During hypothermic cardiopulmonary bypass, cerebral autoregulation seems to be easily disturbed, especially at low nasopharyngeal temperatures.     

The dynamic bubble trap reduces microbubbles in extracorporeal circulation and high intensity transient signals in the middle cerebral artery: a case report

Microemboli during extracorporeal circulation (ECC) might be a reason for postoperative neuropsychological dysfunction. This case report shows that reduction of microbubbles in the arterial line, as well as high intensity transient signals (HITS) in the middle cerebral artery (MCA), could be accomplished by use of a dynamic bubble trap (DBT) during routine coronary artery bypass graft (CABG) surgery in a 63-year-old male. The DBT was placed after the arterial filter, an ultrasound Doppler device was used for detection of microemboli before and after the DBT. HITS were measured by a transcranial ultrasound Doppler in both MCAs. For first 32 min of ECC, the DBTwas excluded; 54 916 microbubbles and 507 HITS were counted. In the next 30 min, blood flow was directed through the DBT. This led to a significant reduction of microbubbles from 55 888 to 18 237; accordingly, only 120 HITS were registered. A DBT, integrated in ECC for routine CABG, effectively reduces air bubbles, thus protecting the cerebrovascular system from microembolization, as demonstrated by lower HITS counts.     

Leucocyte filtration during cardiopulmonary reperfusion in coronary artery bypass surgery.

Postoperative organ dysfunction after cardiac operations has been related to the damaging effects of cardiopulmonary bypass (CPB). These complications are considered to be mediated partly by complement activation and subsequent activation of leucocytes due to the contact between blood and the large nonendothelial surfaces in the bypass circuit. Removal of leucocytes by filtration during the reperfusion period may potentially reduce the postoperative morbidity after CPB. Forty patients undergoing elective, primary coronary artery bypass grafting were randomized to initial identical bypass circuits until the aortic crossclamp was released. Then, the ordinary arterial line filter was closed and either a leucocyte depletion filter (n = 20), or a control filter (n = 20) was incorporated in the circuits during the reperfusion period of CPB. Blood samples were drawn at fixed intervals and analysed for white blood cell and platelet counts, plasma concentration of myeloperoxidase, C3-complement activation products, the terminal complement complex, and interleukins (IL)-6 and -8. The numbers of circulating white blood cells in the leucocyte-depleted group decreased during the reperfusion period from 5.5 (4.8-6.8) to 5.3 (4.4-6.2) x 10(9)/l, and increased in the control group from 6.5 (5.1-8.0) to 7.4 (5.7-9.0) x 10(9)/l. Two hours postoperatively the total white blood cell count in the leucocyte-depleted group was 14.7 (12.1-17.2) x 10(9)/l, and in the control group 17.6 (14.5-20.7) x 10(9)/l. The differences between the groups were statistical significant (p = 0.05). There were no statistically significant differences between the groups with regard to other test parameters or clinical data. We conclude that the use of leucocyte filters during the reperfusion period in elective coronary artery bypass surgery significantly reduced the number of circulating leucocytes, whereas no effects were seen for granulocyte activation measured as myeloperoxidase release, platelet counts, complement activation, or IL-6 and -8 release. The clinical benefit of leucocyte filters in routine or high risk patients remains to be demonstrated and is suggested to be dependent on both the efficacy and the biocompatibility of the filters.     

Can minimized cardiopulmonary bypass systems be safer?

Although a growing body of evidence indicates superiority of minimized cardiopulmonary bypass (mCPB) systems over conventional CPB systems, limited venous return can result in severe fluctuations of venous line pressure which can result in gaseous emboli. In this study, we investigated the influence of sub-atmospheric pressures and volume buffer capacity added to the venous line on the generation of gaseous emboli in the mCPB circuit. Two different mCPB systems (MEC - Maquet, n=7 and ECC.O - Sorin, n=8) and a conventional closed cardiopulmonary bypass (cCPB) system (n=12) were clinically evaluated. In the search for a way to increase volume buffer capacity of mCPB systems, we additionally evaluated the 'Better Bladder' (BB) in a mock circulation by simulating, repeatedly, decreased venous return while measuring pressure and gaseous embolic activity. Arterial gaseous emboli activity during clinical perfusion with a cCPB system was the lowest in comparison to the mCPB systems (312±465 versus 311±421 with MEC and 1,966±1,782 with ECC.O, counts per 10 minute time interval, respectively; p=0.03). The average volume per bubble in the arterial line was the highest in cases with cCPB (12.5±8.3 nL versus 8.0±4.2 nL with MEC and 4.6±4.8 nL with ECC.O; p=0.04 for both). Significant cross-correlation was obtained at various time offsets from 0 to +35 s between sub-atmospheric pressure in the venous line and gaseous emboli activity in both the venous and arterial lines. The in vitro data showed that incorporation of the BB dampens fluctuations of venous line pressure by approximately 30% and decreases gaseous emboli by up to 85%. In conclusion, fluctuations of sub-atmospheric venous line pressure during kinetic-assisted drainage are related to gaseous emboli. Volume buffer capacity added to the venous line can effectively dampen pressure fluctuations resulting from abrupt changes in venous return and, therefore, can help to increase the safety of minimized cardiopulmonary bypass by reducing gaseous microemboli formation resulting from degassing.     

Arterial pH and carbon dioxide tension as indicators of tissue perfusion during cardiac arrest in a canine model.

BACKGROUND AND METHODS: Previous studies have shown that Paco2 and end-tidal CO2 reflect coronary artery perfusion pressures during cardiac arrest. We investigated the relationship of coronary artery perfusion pressure to central arterial pH and Paco2 values during resuscitation from cardiac arrest in a canine model. Twenty-four mongrel dogs were block randomized to three different resuscitation groups after induction of ventricular fibrillation and cardiac arrest: a) standard cardiopulmonary resuscitation (CPR) and advanced life support (n = 8); b) cardiopulmonary bypass (n = 8); or c) open-chest CPR (n = 8). Central arterial blood gases and perfusion pressures were monitored during cardiac arrest and during resuscitation. RESULTS: Prearrest blood gases and hemodynamic values were similar between groups. Sixteen dogs from all three groups were successfully resuscitated. Survivors had significantly higher coronary artery perfusion pressure (p = .03), Paco2 (p = .015), and lower pH (p = .01) values than nonsurvivors. There was no correlation of pH and Paco2 during mechanical external CPR. However, after institution of the different resuscitation techniques, pH and Paco2 each showed a statistically significant correlation (r2 = .50 and .33, respectively) with coronary artery perfusion pressure. CONCLUSIONS: Central arterial pH and Paco2 monitoring during cardiac arrest may reflect the adequacy of tissue perfusion during resuscitation and may predict resuscitation outcome from ventricular fibrillation.     

Effects of ulinastatin treatment on the cardiopulmonary bypass-induced hemodynamic instability and pulmonary dysfunction

OBJECTIVE: To examine the association between decreased release of proinflammatory cytokines in response to urinary trypsin inhibitor pretreatment and decreased myocardial and lung injury after cardiopulmonary bypass. DESIGN: A prospective, randomized, double-blind study. SETTING: University hospital. SUBJECTS: Thirty patients on cardiopulmonary bypass undergoing coronary artery bypass grafting. INTERVENTIONS: Patients received 5000 units/kg intravenous urinary trypsin inhibitor (n = 15) or 0.9% saline (control, n = 15) immediately before aortic cannulation for cardiopulmonary bypass. MEASUREMENT AND MAIN RESULTS: Neutrophil elastase, tumor necrosis factor-alpha, interleukin-6, and interleukin-8 were measured after intubation (T1), immediately before aortic cannulation (T2), after separation from cardiopulmonary bypass (T3), at the end of surgery (T4), and on postoperative days 1 (T5), 3 (T6), and 5 (T7). Simultaneous hematocrit values were obtained at all sample times. Isoenzyme of creatine kinase with muscle and brain subunits, troponin-T, and myosin light chain I were also measured. Various hemodynamic and pulmonary data were obtained perioperatively. Levels of neutrophil elastase and cytokines were corrected for hemodilution. Interleukin-6 and interleukin-8 levels were lower at T3 and T4 in the urinary trypsin inhibitor group than in the control group. Stroke volume index was significantly decreased in the control group at T3, and statistical difference was found between groups at T3 (p < .01). Respiratory index and intrapulmonary shunt were significantly higher in the control group than in the urinary trypsin inhibitor group at T3. Changes in respiratory index and intrapulmonary shunt correlated with interleukin-8 levels at T3 (r = .52, p < 00001; r = .37, p < 0001, respectively) and T4 (r = .44, p < .001; r = .24, p < .05, respectively). Neutrophil elastase levels and cardiac marker responses to coronary artery bypass grafting surgery were similar in both groups. CONCLUSIONS: Prepump administration of urinary trypsin inhibitor attenuates the elevation of interleukin-6 and interleukin-8 release immediately after cardiopulmonary bypass.     

Cardiac surgery in patients with moderate renal impairment

BACKGROUND: There is a paucity of information concerning the results of cardiac surgery in patients with moderate impairment of renal function. We reviewed our recent experience to determine the results of operation and the long-term outcome. METHODS: Since January 1992, we have performed cardiac surgical procedures utilizing total cardiopulmonary bypass on 57 adult patients with preoperative serum creatinine values > or = 2.0 mg/dL and no history of dialysis. Operative procedures done were coronary artery bypass (39 patients), repeated coronary artery bypass (2), valve replacement with or without coronary artery bypass (12), and other procedures (4). RESULTS: No operative deaths occurred. There were 3 hospital deaths. Only 5 patients required perioperative dialysis; in 5 additional patients, chronic dialysis was begun from 4 to 24 months postoperatively. The surviving patients who were not receiving dialysis had a mean creatinine value of 2.4 mg/dL at most recent follow-up. CONCLUSIONS: Adult patients with moderate renal impairment can safely have major cardiac procedures. The majority of patients maintain stable renal function postoperatively. The overall results of cardiac surgery in this patient population are good.     

Evaluation of three hollow-fiber membrane oxygenators without integrated arterial filters for neonatal cardiopulmonary bypass

The cardiopulmonary bypass (CPB) procedure has been shown to be a possible cause of postoperative neurological morbidity for various reasons, including: large amounts of gaseous microemboli (GME) reaching the patient and hypoperfusion of the patient due to "stolen" blood flow. This study used a simulated CPB circuit identical to that in a clinical setting to examine three different hollow-fiber membrane oxygenators without intergrated arterial filters - the Capiox RX05, the Quadrox-i neonatal, and the KIDS D100 - to determine their ability to reduce the number of GME delivered to the neonatal patient and their hemodynamic properties in response to varying flow rates, normothermic vs hypothermic conditions, and open vs closed purge line. The circuit was primed with Ringer's Lactate and then human blood with a hematocrit of 30%. Injections of 5cc bolusses of air were injected into the venous line proximal to the venous reservoir over a thirty-second interval. Six injections were done for each oxygenator at each of the eight different experimental conditions for a total of 64 experiments per oxygenator (192 total injections). A flow probe, pressure transducer, and Emboli Detection and Classification (EDAC) quantifier transducer were positioned both upstream and downstream of the oxygenator to measure differences in each parameter. Results demonstrated that the Capiox RX05 is the most effective oxygenator at reducing the number of microemboli that potentially can be delivered to the neonatal patient. In regards to the hemodynamic properties, the Quadrox-i has the most favorable results, with the lowest mean pressure drop and the best energy retention across the oxygenator.     

Protein C -1641 AA is associated with decreased survival and more organ dysfunction in severe sepsis

OBJECTIVE: Protein C contains an A/G polymorphism at position -1641 and a C/T polymorphism at -1654 associated with risk of deep venous thrombosis. We tested the hypothesis that these polymorphisms are associated with altered outcome in patients having severe sepsis, in which protein C is a central molecule. DESIGN: Prospective cohorts, gene-association study. SETTING: Tertiary care medical/surgical intensive care unit. PATIENTS: We first recruited a derivation cohort of patients having severe sepsis (n = 62). A second replication cohort was similarly defined but larger (n = 402). We tested for biological plausibility in a third cohort of post-cardiopulmonary bypass patients (n = 61). INTERVENTIONS: Patients were genotyped at protein C -1641 and -1654. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was survival in cohorts 1 and 2 and postoperative serum interleukin-6 concentration in cohort 3. Severity of individual organ dysfunctions and systemic inflammation were secondary outcome variables. In the first derivation cohort, the protein C -1641 AA genotype was associated with decreased 28-day survival (p < .05). This finding was confirmed in the much larger replication cohort of patients having severe sepsis (p = .028). In addition, the protein C -1641 AA genotype was associated with significantly more organ dysfunction and more clinical evidence of systemic inflammation (p < .05). Furthermore, the -1641 AA genotype was associated with increased serum interleukin-6 at 4 and 24 hrs after cardiopulmonary bypass (p = .024). There was no association of -1654 A/G with phenotype in any cohort. CONCLUSIONS: Protein C -1641 AA genotype is associated with decreased survival, more organ dysfunction, and more systemic inflammation in patients having severe sepsis and with increased interleukin-6 levels after cardiopulmonary bypass surgery.     

CT血管造影分析体外循环与非体外循环冠状动脉旁路移植后的桥血管通畅率

背景:近年来,非体外循环冠状动脉旁路移植后桥血管通畅率是否与传统的体外循环冠状动脉旁路移植相同存在争议.目的:探讨体外循环与非体外循环冠状动脉旁路移植后桥血管时间通畅率的差异性.方法:选取同一操作者行体外循环冠状动脉旁路移植患者100例,按其临床特征及桥血管病变危险因素匹配抽取非体外循环冠状动脉旁路移植患者137例.采用64排多螺旋CT血管造影分析冠脉搭桥后1个月,1年,2年,3年,4年的桥血管通畅情况.结果与结论:共对641条桥血管进行评价,两组中左侧乳内动脉桥血管时间通畅率均高于大隐静脉桥,两组左侧乳内动脉桥和人隐静脉桥血管时间通畅率比较差异均无显著性意义.说明非体外循环与体外循环冠状动脉旁路移植后患者桥血管时间通畅率相似,对于某些适当的患者来说,非体外循环冠状动脉旁路移植不失为一个良好的选择.